Diabetes and Glycemic Control
Diabetes mellitus is a disease of major global importance, increasing in frequency at almost epidemic rates, such that the worldwide prevalence as of 2006 was 170 million people and has been predicted to at least double over the next 10-15 years. Diabetes is characterized by a chronically raised blood glucose concentration (hyperglycemia), due to a relative or absolute lack of the pancreatic hormone, insulin. Within the healthy pancreas, beta cells, located in the islets of Langerhans, continuously produce and secrete insulin according to the blood glucose levels, maintaining near constant glucose levels in the body.
Much of the burden of the disease to the patient and to health care resources is due to the long-term tissue complications, which affect both the small blood vessels (microangiopathy, causing eye, kidney and nerve damage) and the large blood vessels (causing accelerated atherosclerosis, with increased rates of coronary heart disease, peripheral vascular disease and stroke). The Diabetes Control and Complications Trial (DCCT) demonstrated that development and progression of the chronic complications of diabetes are greatly related to the degree of altered glycemia as quantified by determinations of glycohemoglobin (HbA1c). [DCCT Trial, N Engl J Med 1993; 329: 977-986, UKPDS Trial, Lancet 1998; 352: 837-853. BMJ 1998; 317, (7160): 703-13 and the EDIC Trial, N Engl J Med 2005; 353, (25): 2643-53]. Thus, maintaining normoglycemia by frequent glucose measurements and adjustment of insulin delivery accordingly is of utmost importance.
Insulin pumps deliver rapid acting insulin 24 hours a day through a catheter placed under the skin. The total daily insulin dose is divided into basal and bolus doses.
Insulin bolus doses are delivered before or after meals to counteract carbohydrates loads or during episodes of high blood sugar levels.
Basal insulin is delivered continuously over 24 hours to maintain blood glucose levels in range between meals and overnight. The basal rate regulates the food-independent insulin requirement, and is predominantly dependent on hepatic gluconeogenesis, physical activity, sleep-awake circadian cycle, etc.
Generally, available pumps offer the user the ability to set a variety of basal profiles (e.g., 4-8 different profiles). The user selects a profile or profiles that best match his/her basal insulin needs. Some pumps enable the user to program a basal profile in hourly intervals, according to the user's specific daily routine and circadian basal insulin needs. Some pumps also have a temporary basal rate apparatus that is useful to manage BG levels during unusual short-term activities or conditions (e.g. unplanned physical activity).
Referring to FIG. 1, a graph of an exemplary basal pattern used, for example, with currently marketed insulin pumps is shown. The basal pattern is a 24 hour sequence of basal rates a patient is supposed to receive such that the patient is administered insulin at all times. The basal rate is generally measured in units per hour and may be changed in 30 minute intervals. However, as shown in the example, in some embodiments, the patterns used are typically divided into 3-6 segments, each segment specifying a single rate. The depicted pattern in the example of FIG. 1 provides higher insulin dosages in the evening and early morning, in conformity with the relative insulin resistance of the user during those hours.
In some embodiments, a patient may have set his/her pump on this pattern to determine through a process of trial and error an insulin infusion pattern that substantially achieves euglycemia. Such a trial-and-error approach may involve numerous hyperglycemic and hyperglycemic events.
Some studies have shown that patient age has been associated with use of different basal insulin infusion distributions. For example, in adolescents and young adults, decreased insulin sensitivity is seen, particularly in the early morning (dawn phenomenon) and to a lesser extent, in the late afternoon (dusk phenomenon). This leads to a typical two-waved basal rate profile (referred to as “dawn-dusk” pattern). High glucose values caused by a nocturnal hypoglycemia with a rebound effect (so called Somogyi phenomenon) is also evident, but is more common in MDI than in continuous subcutaneous insulin infusion (CSII). Results from the PedPump Study Group, Conrad et al. and Boland et al. also noted that younger children often need higher doses of basal insulin before midnight (between 21:00 hours and midnight). (Pediatric Diabetes 2006: 7 (Suppl. 4): 25-31, 2006).